This invention pertains to new biocompatible polymers, a process for their preparation and compositions containing them.
Known in the prior art are polymer derivatives of dextrans obtained by substitution by carboxymethyl, carboxymethyl-benzylamide and carboxymethyl-benzylamide-sulfonate residues. These polymers, the process for their preparation and their properties, are described in French Patent No. 2,461,724 as well as in U.S. Pat. No. 4,740,594. Among these polymers, certain of them imitate the properties of heparin and can be used as plasma substitution products because of their anticoagulant and anticomplement properties. Others imitate a different property of heparin which consists of a stabilization, protection and potentiation of the in vitro biological activity of the growth factors of the FGF family (Tardieu et al., Journal of Cellular Physiology, 1992, 150, pages 194 to 203). Furthermore, French Patent No. 2,644,066 describes the use of carboxymethyl-benzylamide-sulfonate derivatives of dextran, referred to as CMDBS, alone or associated with FGFs, for cicatrization.
More recently, French Patent Nos. 2,718,023, 2,718,024 and 2,718,026 proposed the use of polymers capable of protecting, stabilizing and potentiating growth factors that have an affinity for heparin, such as the fibroblast growth factors or FGF and Transforming Growth Factor beta (TGFxcex2), as a drug for the treatment of lesions of the gastrointestinal tract, nervous system and muscle tissues, respectively. To illustrate this protective effect of the CMBDS dextran derivatives, these patents present the results of the proteolytic digestion by trypsin of FGF1, FGF2 or TGFxcex2. These properties of protection, stabilization and potentiation of the growth factors with an affinity for heparin enabled characterization of a new class of polymers, designated as HBGFPP to indicate xe2x80x9cHeparin-Binding Growth Factor Protector and Potentiatorxe2x80x9d, that exhibit cicatrizing and repair activities in relation to muscle, nervous and gastrointestinal tract tissues, and which are devoid of anticoagulant activity at the doses employed.
In addition to the above HBGFPP applications, French Patent No. 2,718,025 proposes the use of these polymers as drugs for the treatment of inflammations. This anti-inflammatory activity is illustrated by the in vitro inhibitory action against proteolytic enzymes implicated in the inflammatory reaction such as leukocyte elastase or plasmin and in vivo by histological studies demonstrating a reduced inflammatory cellular reaction in tissues treated by CMDBS dextran derivatives.
However, these CMDBS dextran derivatives are compounds which are difficult to synthesize and present the risk of salting out residues that are known for their toxic effects such as benzylamine. Furthermore, the applications of the HBGFPP and thus of the CMDBS proposed in the prior art are limited solely to the repair and cicatrization of certain tissues.
The invention relates to a biocompatible polymer constituted by a sequence of identical or different components of the general formula (I): AaXxYy, in which A represents a monomer, X represents a carboyxl group fixed on a monomer A, Y represents a sulfate or sulfonate group fixed on a monomer A; a represents the number of monomers A, x represents the substitution rate of the set of monomers A by the groups X, y represents the substitution rate of the set of monomers A by the groups Y. The invention also relates to the pharmaceutical or diagnostic compositions containing at least one polymer of general formula (I).